Preventie van postoperatieve wondinfecties

Initiatief: NVVH / SRI Aantal modules: 26

Darmvoorbereiding

Uitgangsvraag

What is the effect of different methods of bowel preparation on the incidence of surgical site infections (SSI), anastomotic leakage (AL) and mortality in patients undergoing elective colorectal surgery?

Aanbeveling

Overweeg om patiënten voorafgaand aan colorectale chirurgie, ter preventie van postoperatieve wondinfecties (en naadlekkages), met de volgende darmvoorbereiding:

  • Alleen orale antibiotica, of
  • Orale antibiotica in combinatie met mechanische darmvoorbereiding

Bespreek met patiënten de voor- en nadelen van mechanische darmvoorbereiding.

 

Behandel patiënten voorafgaand aan colorectale chirurgie niet met alleen mechanische darmvoorbereiding met als doel preventie van postoperatieve wondinfecties en naadlekkages.

 

Voor advies t.a.v. keuze van het middel, dosering en duur van de behandeling verwijzen wij naar de lokale SWAB-richtlijnen. Deze aanbeveling is in aanvulling op de intraveneuze chirurgische antibiotische profylaxe (indien geïndiceerd).

Overwegingen

Summary of the evidence

The network meta-analysis by Jalalzadeh et al. (2022) showed the effect of different types of bowel preparation on the rates of surgical site infections, anastomotic leakage, and mortality for patients undergoing elective colorectal surgery. The results showed a significant reduction of SSI when using MBP-OA compared with only MBP or no preparation and for OA alone compared with MBP. MBP-OA and OA showed comparable effectiveness (for SSI reduction NNT 13 and 18, respectively). There was no difference in effect between MBP and no preparation.

 

Overall, the certainty of evidence was graded as moderate to low because of imprecision of the results and risk of bias. Furthermore, MBP-OA and OA may both be effective for the prevention of anastomotic leakage, whereas MBP was not.

 

There was no clear association between the method of bowel preparation and all-cause mortality rate. Only in a sensitivity analysis of studies that focused on laparoscopic surgery or a mixed laparoscopic/open population, MBP-OA seemed more effective than other methods.

 

International guidelines

The findings are of added value to existing guideline recommendations. The results are partly in line with current international guidelines but give an important new perspective. WHO (2018) and NICE (2019) guidelines both advise against the use of only MBP as routine preparation. The WHO advises MBP-OA in colorectal surgery. However, both guidelines did not include studies investigating the effect of OA alone. The NICE guidelines acknowledge this limitation and state that their current guideline should be updated with newly published evidence, including studies investigating the effect of OA alone. The current guideline of the CDC (O’Hara 2018) does not mention bowel preparation. Previous, non-network meta-analyses have shown results in favor of MBP-OA compared to MBP (Rollins 2019) and no clear difference between MBP and no preparation (Güenaga 2011). These results are still in line with present study but lack the relative effect of OA alone. One of the trials investigating the effect of OA alone (Mulder 2020), ended prematurely due to results of a new non-randomized study favoring OA (Mulder 2019). The authors no longer considered clinical equipoise.

 

A recent NMA (Woodfield 2022) concludes that OA without MBP shows the greatest reduction in SSI. This is not in line with our findings. Current evidence from present NMA shows that effectiveness of OA alone does not significantly differ from that of MBP-OA (RR 0.81, 95% CI 0.54 – 1.19). Our results support the use of OA alone, and we do not find MBP-OA to be superior to OA. The most recent NMA has not included some of these new RCTs, which explains the difference in results. Some studies were published after the search date, others were excluded for unknown reasons. An earlier NMA (Toh 2018) has identified a knowledge gap with respect to effectiveness of OA as few studies compared OA alone to MBP-OA or no preparation. We included four additional RCTs investigating OA as sole intervention without MBP; all published since 2020. One RCT compared OA alone to MBP-OA (Suzuki 2020) and three studies compared OA alone to no preparation (Arezzo 2021, Espin-Basany 2020, Mulder 2020). 

 

Subgroup: minimal invasive procedures

In recent years, minimally invasive procedures are widely performed and a distinction between effects of the various bowel preparations in open and laparoscopic procedures could be very helpful in clinical practice. Therefore, an additional sensitivity analysis was performed, excluding RCTs with only open surgical procedures. In the remaining cohort for analysis, still 40% of the procedures were open procedures. It was not possible to attribute SSI to either laparoscopic or open surgery among these mixed studies as such details were not supplied in the original publications. Therefore, it is not possible to draw firm recommendations on the various bowel preparation methods between open and laparoscopic procedures. More studies including only laparoscopic procedures are needed to draw definite conclusions.

 

Patient preferences

Analysis of effectivity does not take the discomfort and possible harms (e.g., electrolytes imbalance and dehydration) of MBP into consideration nor its practical concerns such as early hospital admission and discomfort for the patient. The harms and benefits should be carefully weighed with patients, ideally using the principles of shared decision making justifying the additional value of MBP to OA.

 

Pros and cons of mechanical bowel preparation

Pros may include:

  • Improvement of operative handling of the bowels

Cons may include:

  • Bad taste and large amount of solution
  • Increase of bowel movements over period of hours
  • Nausea and vomiting
  • Electrolyte imbalance
  • Temporary decrease of absorption of other medication

Resource use

There are no cost-effective studies available.

 

Sustainability, feasibility, and implementation

There seems to be no issues regarding the feasibility for implementation in clinical practice. Mechanical bowel preparation is often done since no feces can enter the abdominal cavity. Mechanical preparation prior to surgery also gives a better view that may be beneficial during surgery. This may be a barrier for applying OA alone.

 

Rationale of the recommendation

Present findings revealed that MBP-OA and OA alone reduce SSI and likely reduce AL rates compared to no bowel preparation and that MBP-OA results in little to no difference in SSI and AL rates compared to OA alone. For the consideration of adding MBP to OA, one should consider patient preferences, using principles of shared decision making, explaining possible discomfort or harms (e.g., electrolytes imbalance and dehydration), and practical issues.

Onderbouwing

Surgical site infections (SSI) and anastomotic leakage (AL) are serious complications after colorectal surgery and associated with high morbidity, mortality, and costs. Incidence of 5-25% for SSI and 3-12% for AL have been reported. Bowel preparation may prevent a large proportion of SSI and can be performed using mechanical bowel preparation (MBP), oral antibiotics alone (OA) and a combination of both (MBP-OA). Here, we provide an up-to-date evaluation on the effect of different methods of bowel preparation on surgical site infections, anastomotic leakage, and mortality after elective colorectal surgery.

Surgical site infections (SSI)

MBP-OA versus OA

Low

GRADE

The evidence suggests that mechanical bowel preparation combined with oral antibiotics results in little to no difference in surgical site infections compared to only oral antibiotics in patients undergoing elective colorectal surgery.

 

MBP-OA versus MBP

Moderate

GRADE

Mechanical bowel preparation combined with oral antibiotics likely reduces surgical site infections compared to only mechanical bowel preparation in patients undergoing elective colorectal surgery.

 

MBP-OA versus None

Moderate

GRADE

Mechanical bowel preparation combined with oral antibiotics likely reduces surgical site infections compared with no preparation in patients undergoing elective colorectal surgery. 

 

OA versus MBP

Low

GRADE

The evidence suggests only oral antibiotics reduces surgical site infections compared to only mechanical bowel preparation in patients undergoing elective colorectal surgery.

 

OA versus None

Low

GRADE

The evidence suggests only oral antibiotics reduces surgical site infections compared to no preparation in patients undergoing elective colorectal surgery.

 

 

MBP versus None

Low

GRADE

 The evidence suggests that only mechanical bowel preparation results in little to no difference in surgical site infections compared to no preparation in patients undergoing elective colorectal surgery.

 

Anastomotic leakage

 

MBP-OA versus OA

Low

GRADE

The evidence suggests that mechanical bowel preparation combined with oral antibiotics results in little to no difference of anastomotic leakage compared to only oral antibiotics in patients undergoing elective colorectal surgery.

 

MBP-OA versus MBP

Moderate

GRADE

Mechanical bowel preparation combined with oral antibiotics likely reduces anastomotic leakage compared to only mechanical bowel preparation in patients undergoing elective colorectal surgery.

 

MBP-OA versus None

Low

GRADE

The evidence suggests mechanical bowel preparation combined with oral antibiotics reduces anastomotic leakage compared to no preparation in patients undergoing elective colorectal surgery.

 

OA versus MBP

Low

GRADE

The evidence suggests that only oral antibiotics results in little to no difference of anastomotic leakage compared to only mechanical bowel preparation in patients undergoing elective colorectal surgery.

 

OA versus None

Low

GRADE

The evidence suggests that only oral antibiotics may result in a slight reduction of anastomotic leakage compared with no preparation in patients undergoing elective colorectal surgery.

 

MBP versus None

Low

GRADE

The evidence suggests that mechanical bowel preparation results in little to no difference in anastomotic leakage compared to no preparation in patients undergoing elective colorectal surgery.

 

Mortality

 

MBP-OA versus OA

Very low

GRADE

The evidence is very uncertain about the effect of mechanical bowel preparation combined with oral antibiotics on mortality compared with only oral antibiotics in patients undergoing elective colorectal surgery.

 

MBP-OA versus MBP

Very low

GRADE

The evidence is very uncertain about the effect of mechanical bowel preparation combined with oral antibiotics on mortality compared to only mechanical bowel preparation in patients undergoing elective colorectal surgery.

 

MBP-OA versus None

Very Low

GRADE

The evidence is very uncertain about the effect of mechanical bowel preparation combined with oral antibiotics on mortality compared to no bowel preparation in patients undergoing elective colorectal surgery.

 

OA versus MBP

Very low

GRADE

The evidence is very uncertain about the effect of only oral antibiotics on mortality compared to mechanical bowel preparation in patients undergoing elective colorectal surgery.

 

OA versus None

Very low

GRADE

The evidence is very uncertain about the effect of only oral antibiotics on mortality compared to no preparation in patients undergoing elective colorectal surgery.

 

MBP versus None

Very Low

GRADE

The evidence is very uncertain about the effect of mechanical bowel preparation on mortality compared to no preparation among patients undergoing elective colorectal surgery.

 

Description of studies

Forty-eight RCTs were included in the analysis of the literature, involving 13,611 patients. In total, 23 RCTs compared MBP-OA and MBP (Abis, 2019; Anjum, 2017; Espin-Basany, 2005; Coppa, 1988; Hata, 2016; Horie, 2007; Ikeda, 2016; Ishida, 2001; Kobayashi, 2007; Lau, 1988; Lewis, 2002; Oshima, 2013; Papp, 2021; Playforth, 1988; Reynolds, 1989; Roos, 2011; Rybakov, 2021; Sadahiro, 2013; Schardey, 2020; Stellato, 1990; Takesue, 2000; Taylor, 1994; Uchino, 2019), sixteen RCTs compared MBP and no preparation (Bertani, 2011; Bhat, 2016; Bhattacharjee, 2015; Bretagnol, 2010; Bucher, 2005; Burke, 1994; Contant, 2007; Fa-Si-Oen, 2005; Jung, 2007; Mai-Phan, 2019; Miettinen, 2000; Pena-Soria, 2008; Platell, 2006; Ram, 2005; Sasaki, 2012; Watanabe, 2010), five RCTs compared OA with no preparation (Arezzo, 2021; Espin-Basany, 2020; Hanel, 1980; Mulder, 2020; Viddal, 1980), three RCTs compared OA and MBP-OA (Suzuki, 2020; Zmora, 2003; Zmora, 2006) and one RCT compared MBP-OA and no preparation (Koskenvuo, 2019).

 

The following solutions were used for MBP, alone or in combination with others: polyethylene glycol solution (n=24), sodium picosulfate (n=10), sodium phosphate (n=8), magnesium citrate (n=5), bisacodyl (n=2), mannitol (n=1), and senna (n=1). Risk of bias was assessed with the Cochrane Risk of Bias-2 (RoB2) tool. The reported outcomes were surgical site infections.

 

The protocols regarding OA in the 32 studies varied greatly. Aminoglycosides (e.g., kanamycin, tobramycin and neomycin) or erythromycin were used in 27 out of 32 studies, of which in fourteen studies in combination with metronidazole. OA were usually started the day before surgery. Alternative protocols span from three days preoperative until postoperative day seven, ranging from two till four times a day.

 

For intravenous surgical antimicrobial prophylaxis, cephalosporins (1 to 2 grams) alone or in combination with metronidazole (0.5 to 1 grams), or flomoxef (a cephamycin, 1 gram) were often used. Redosing of SAP during surgery was performed in fifteen out of 48 studies, if surgery lasted longer than two to four hours depending on the half-life of antibiotics used.

 

1. Surgical site infections (SSI)

A network meta-analysis was carried out to investigate the effect of the different treatment modalities on SSI. In total, 47 RCTs contributed to the overall NMA. A network graph, including all studies is presented in figure 1. The forest plot of the results of the different preparation methods compared to no preparation is shown in figure 2.

Figure 1. Network graph of all studies for outcome surgical site infections in network meta-analysis (Jalalzadeh, 2022)

 

Figure 2. Forest plot shows the pooled estimates from the included studies, comparing different bowel preparation methods with no preparation for outcome total SSI. (Jalalzadeh, 2022)

 

1.1 MBP-OA versus OA

In total, two studies (n= 631) contributed with a direct comparison to the NMA investigating the effect of MBP-OA versus OA on SSI (Suzuki, 2020; Zmora, 2003). The overall network RR was 0.81 (95% CI 0.54, 1.19), a non-significant nor clinically relevant difference between groups.

 

1.2 MBP-OA versus MBP

In total, twenty-three studies (n=6197) contributed with a direct comparison to the NMA investigating the effect of MBP-OA versus MBP on SSI (Abis, 2019; Anjum, 2017; Coppa, 1988; Espin-Basany, 2005; Hata, 2016; Horie, 2007; Ikeda, 2016; Ishida, 2001; Kobayashi, 2007; Lau, 1988; Lewis, 2002; Oshima, 2013; Papp, 2021; Playforth, 1988; Reynolds, 1989; Roos, 2011; Rybakov, 2021; Sadahiro, 2013; Schardey, 2020; Stellato, 1990; Takesue, 2000; Taylor, 1994; Uchino, 2019). The overall network RR was 0.55 (95% CI 0.46, 0.65), a significant and clinically relevant difference favoring MBP-OA.

 

1.3 MBP-OA versus no preparation

In total, one study (n=396) contributed with a direct comparison to the NMA investigating the effect of MBP-OA versus no preparation on SSI (Koskenvuo, 2019). The overall network RR was 0.57 (95% CI 0.45, 0.73), with a corresponding number needed to treat of 13, which is a significant and clinically relevant difference favoring MBP-OA.

 

Clarification of the number needed to treat calculation

CER*                  = 561 / 3229     = 0.174

TER**                 = CER x RR       = 0.174 x 0.57                = 0.099

ARR***               = CER – TER     = 0.174 – 0.099              = 0.075

NNT                   = 1 / ARR          = 1 / 0.075                      = 13

 

*CER (event rate in control group) = 561 / 3229 = 0.174

**TER (event rate in treatment group)

***ARR (absolute risk reduction)

 

1.4 OA versus MBP

There were no studies that contributed with a direct comparison to the NMA investigating the effect of OA versus MBP on SSI. Therefore, indirect estimates of the comparison of OA versus MBP in the NMA were reported. The overall network RR was 0.68 (95% CI 0.46, 0.99), a significant and clinically relevant difference favoring OA.

 

1.5 OA versus no preparation

In total, five studies (n=927) contributed with a direct comparison to the NMA investigating the effect of OA versus no preparation on SSI (Mulder, 2020; Arezzo, 2021; Espin-Basany, 2020; Hanel, 1980; Viddal, 1980). The overall network RR was 0.71 (95% CI 0.50, 1.01), with a corresponding number needed to treat of 18, which is a non-significant but clinically relevant difference favoring OA.

 

Clarification of the number needed to treat calculation

CER*                  = 561 / 3229      = 0.174

TER**                 = CER x RR        = 0.174 x 0.68                = 0.118

ARR***               = CER – TER      = 0.174 – 0.118              = 0.056

NNT                   = 1 / ARR           = 1 / 0.056                      = 18

 

*CER (event rate in control group) = 561 / 3229 = 0.174

**TER (event rate in treatment group)

***ARR (absolute risk reduction)

 

1.6 MPB versus no preparation

In total, sixteen studies (n=5211) contributed with a direct comparison to the NMA investigating the effect of MPB versus no preparation on SSI (Bertani, 2011; Bhat, 2016; Bhattacharjee, 2015; Bretagnol, 2010; Bucher, 2005; Burke, 1994; Contant, 2007; Fa-Si-Oen, 2005; Jung, 2007; Mai-Phan, 2019; Miettinen, 2000; Pena-Soria, 2008; Platell, 2006; Ram, 2005; Sasaki, 2012; Watanabe, 2010). The overall network RR was 1.04 (95% CI 0.86, 1.26), which is a non-significant nor clinically relevant difference between groups; corresponding number needed to treat is negative and number needed to harm is 111.

 

Clarification of the number needed to treat calculation

CER*                 = 561 / 3229      = 0.174

TER**                = CER x RR        = 0.174 x 1.05                = 0.183

ARR***              = CER – TER      = 0.174 – 0.183              = -0.009

NNT                  = 1 / ARR           = 1 / -0.009                    = negative

 

ARI****             = TER – CER      = 0.183 – 0.174              = 0.009

NNH                 = 1 / ARI            = 1 / 0.009                      = 111

 

*CER (event rate in control group) = 561 / 3229 = 0.174

**TER (event rate in treatment group)

***ARR (absolute risk reduction)

****ARI (absolute risk difference)

 

2. Anastomotic leakage

A network meta-analysis was carried out to investigate the effect of the different treatment modalities on anastomotic leakage. In total, 38 RCTs contributed to the overall NMA. A network graph, including all studies is presented in figure 3. The forest plot of the results of the different preparation methods compared to no preparation is shown in figure 4.

 

 

Figure 3. Network graph of all studies for outcome anastomotic leakage in network meta-analysis (Jalalzadeh, 2022)

 

 

Figure 4. Forest plot shows the pooled estimates from the included studies, comparing different bowel preparation methods with no preparation for outcome anastomotic leakage. (Jalalzadeh, 2022)

 

2.1   MBP-OA versus OA

In total, two studies (n= 631) contributed with a direct comparison to the NMA investigating the effect of MBP-OA versus OA on AL (Suzuki, 2020; Zmora, 2003). The overall network RR was 0.70 (95% CI 0.46, 1.08), a non-significant but clinically relevant difference favoring MBP-OA.

 

2.2   MBP-OA versus MBP

In total, eighteen studies (n=4585) contributed with a direct comparison to the NMA investigating the effect of MBP-OA versus MBP on AL (Abis, 2019; Anjum, 2017; Coppa, 1988; Espin-Basany, 2005; Hata, 2016; Horie, 2007; Ikeda, 2016; Ishida, 2001; Lau, 1988; Papp, 2021; Playforth, 1988; Roos, 2011; Rybakov, 2020; Sadahiro, 2014; Schardey, 2020; Stellato, 1990; Takesue, 2000; Taylor, 1994;). Espin-Basany (2005) reported zero AL in both arms and was thus excluded from the NMA, leaving 17 studies in the final NMA (figure 2).

Node splitting the results showed this comparison had significant inconsistencies between direct and indirect evidence. The direct evidence has higher quality of evidence, thus we valued the direct comparison over the indirect comparison (and use this for our conclusion).

The overall direct RR was 0.55 (95% CI 0.40, 0.76), a significant and clinically relevant difference favoring MBP-OA.

 

2.3   MBP-OA versus no preparation

In total, one study (n=396) contributed with a direct comparison to the NMA investigating the effect of MBP-OA versus no preparation on AL (Koskenvuo, 2019). The overall network RR was 0.56 (95% CI 0.39, 0.81), a significant and clinically relevant difference favoring MBP-OA.

 

2.4 OA versus MBP

There were no studies that contributed with a direct comparison to the NMA investigating the effect of OA versus MBP on AL. Therefore, only the indirect estimates of the comparison between OA and MBP was reported. The overall network RR was 0.87 (95% CI 0.61, 1.23), a non-significant nor clinically relevant difference between groups.

 

2.5 OA versus no preparation

In total, four studies (n=860) contributed with a direct comparison to the NMA investigating the effect of OA versus no preparation on AL (Arezzo, 2021; Espin-Basany, 2020; Mulder, 2020; Vidal, 1980). Vidal (1980) reported zero AL in both arms and was thus excluded from the NMA, leaving three studies in the final NMA (figure 2). The overall network RR was 0.80 (95% CI 0.62, 1.02), a non-significant but clinically relevant difference favoring OA.  

 

2.6 MPB versus no preparation

In total, sixteen studies (n=5211) contributed with a direct comparison to the NMA investigating the effect of MBP versus no preparation on AL (Bertani, 2011; Bhat, 2016; Bhattacharjee, 2015; Bretagnol, 2010; Bucher, 2005; Burke, 1994; Contant, 2007; Fa-Si-Oen, 2005; Jung, 2007; Mai-Phan, 2019; Miettinen, 2000; Pena-Soria, 2008; Platell, 2006; Ram, 2005; Sasaki, 2012; Watanabe, 2010). Watanabe (2010) reported zero AL in both arms and was thus excluded from the NMA, leaving 15 studies in the final NMA (figure 2).

Node splitting the results showed this comparison had significant inconsistencies between direct and indirect evidence. The direct evidence has higher quality of evidence, thus we valued the direct comparison over the indirect comparison (and use this for our conclusion).

The overall direct RR was 0.85 (95% CI 0.71, 1.18), a non-significant nor clinically relevant difference.

 

3. Mortality

A network meta-analysis was carried out to investigate the effect of the different treatment modalities on mortality. In total, 20 RCTs contributed to the overall NMA. A network graph, including all studies is presented in figure 3.

 

 

Figure 5. Network graph of all studies for outcome mortality in network meta-analysis (Jalalzadeh, 2022)

 

Figure 6. Forest plot shows the pooled estimates from the included studies, comparing different bowel preparation methods with no preparation for outcome mortality. (Jalalzadeh, 2022)

 

3.1   MBP-OA versus OA

In total, two studies (n= 631) contributed with a direct comparison to the NMA investigating the effect of MBP-OA versus OA on mortality (Suzuki, 2020; Zmora, 2003). Suzuki (2020) reported zero deaths in both arms and was thus excluded from the NMA, leaving one study in the final NMA (figure 3). The overall network RR was 0.61 (95% CI 0.17, 2.26), a non-significant nor clinically relevant difference between groups.

 

3.2   MBP-OA versus MBP

In total, eleven studies (n=3062) contributed with a direct comparison to the NMA investigating the effect of MBP-OA versus MBP on mortality (Abis, 2019; Coppa, 1988; Horie, 2007; Ikeda, 2016; Lewis, 2002; Papp, 2021; Playforth, 1988; Roos, 2011; Schardey, 2020; Stellato, 1990; Taylor, 1994). Ikeda (2016) and Horie (2007) reported zero deaths in both arms and were excluded from the NMA, leaving 9 studies in the final NMA (figure 3). The overall network RR was 0.97 (95% CI 0.58, 1.62), a non-significant nor clinically relevant difference between groups.

 

3.3   MBP-OA versus no preparation

In total, one study (n=396) contributed with a direct comparison to the NMA investigating the effect of MBP-OA versus no preparation on mortality (Koskenvuo, 2019). The overall network RR was 0.96 (95% CI 0.49, 1.87), a non-significant nor clinically relevant difference between groups.

 

3.4   OA versus MBP

There were no studies that contributed with a direct comparison to the NMA investigating the effect of OA versus MBP on mortality. Therefore, indirect estimates of the comparison of OA versus MBP in the NMA were reported. The overall network RR was 1.69 (95% CI 0.44, 6.25), a non-significant nor clinically relevant difference between groups.

 

3.5   OA versus no preparation

In total, two studies (n=282) contributed with a direct comparison to the NMA investigating the effect of OA versus no preparation on mortality (Arezzo, 2021; Mulder, 2020). Mulder (2020) reported zero deaths in both arms and was thus excluded from the NMA, leaving one study in the final NMA (figure 3). The overall network RR was 1.57 (95% CI 0.40, 6.06), a non-significant nor clinically relevant difference between groups.

 

3.6   MPB versus no preparation

In total, fourteen studies (n=5090) contributed with a direct comparison to the NMA investigating the effect of MBP versus no preparation on mortality (Bhat, 2016; Bertani, 2011; Bhattacharjee, 2015; Bretagnol, 2010; Bucher, 2005; Burke, 1994; Contant, 2007; Fa-Si-Oen, 2005; Jung, 2007; Mai-Phan, 2019; Miettinen, 2000; Pena-Soria, 2008; Platell, 2006; Ram, 2005). Mai-Phan (2019), Bhat (2016), Bertani (2011), Bucher (2005), Fa-Si-Oen (2005) and Miettienen (2000) reported zero events in both arms, leaving eight studies in the final NMA. The overall RR was 0.93 (95% CI 0.60, 1.44), a non-significant nor clinically relevant difference between groups.

 

Level of evidence of the literature

The GRADE approach for rating the certainty of estimates of treatment effects was used. Since all included studies are randomized controlled trials, the rating for the GRADE starts high for all comparisons. Each comparison can be downgraded due to one of the following reasons: risk of bias: the quality assessment of the individual studies is presented in the risk of bias tables; inconsistency: similarity of point estimates, extent of overlap of confidence intervals, and statistical criteria including tests of heterogeneity and I; imprecision: For point estimates with 95%CIs that crosses the null-effect threshold and boundaries for clinical decision making we downgraded with one or two dimensions. If the boundaries are not crossed, we did not downgrade. Publication bias: The comparison-adjusted funnel plot showed no sign of small-study effects (see funnel plot diagrams). 

 

If only direct or indirect evidence is available for a given comparison, the network quality rating will be based on that estimate. When, for a particular comparison, both direct and indirect evidence are available, we used the highest of the two quality ratings as the quality rating for the NMA estimate. The quality of the network estimate can be upgraded if precision is greater than direct or indirect estimates.

 

Table 2. Level of evidence per comparison for surgical site infection, anastomotic leakage, and mortality.

 

 

Reasons for downgrading

Direct evidence

Indirect evidence

Network meta-analysis

Surgical site infections

 

 

 

MBP-OA vs. OA

-2 imprecision

-1 risk of bias

-2 imprecision

-1 risk of bias

-2 imprecision

-1 risk of bias

MBP-OA vs. MBP

-1 risk of bias

-1 imprecision

-1 risk of bias

-1 risk of bias

MBP-OA vs. None

 

-2 imprecision

-1 risk of bias

-1 risk of bias

-1 risk of bias

OA vs. MBP

N.a.

 

-1 imprecision

-1 risk of bias

-1 imprecision

-1 risk of bias

OA vs. None

 

-1 imprecision

-1 risk of bias

-1 imprecision

-1 risk of bias

-1 imprecision

-1 risk of bias

MBP vs. None

 

-1 imprecision

-1 risk of bias

-2 imprecision

-1 risk of bias

-1 imprecision

-1 risk of bias

Anastomotic leakage

 

 

 

MBP-OA vs. OA

-2 imprecision

-1 risk of bias

-1 imprecision

-1 risk of bias

-1 imprecision

-1 risk of bias

MBP-OA vs. MBP

 

-1 risk of bias

-2 imprecision

-1 risk of bias

-1 risk of bias

MBP-OA vs. None

 

-2 imprecision

-1 risk of bias

-1 imprecision

-1 risk of bias

-1 imprecision

-1 risk of bias

OA vs. MBP

N.a

 

-1 imprecision

-1 risk of bias

-1 imprecision

-1 risk of bias

OA vs. None

 

-1 imprecision

-1 risk of bias

-1 imprecision

-1 risk of bias

-1 imprecision

-1 risk of bias

MBP vs. None

 

-1 imprecision

-1 risk of bias

-1 imprecision

-1 risk of bias

-1 imprecision

-1 risk of bias

Mortality

 

 

 

MBP-OA vs. OA

 

-2 imprecision

-1 risk of bias

-2 imprecision

-1 risk of bias

-2 imprecision

-1 risk of bias

MBP-OA vs. MBP

 

-2 imprecision

-1 risk of bias

-2 imprecision

-1 risk of bias

-2 imprecision

-1 risk of bias

MBP-OA vs. None

 

N.a.

-2 imprecision

-1 risk of bias

-2 imprecision

-1 risk of bias

OA vs. MBP

 

-2 imprecision

-1 risk of bias

-2 imprecision

-1 risk of bias

-2 imprecision

-1 risk of bias

OA vs. None

 

-2 imprecision

-1 risk of bias

-2 imprecision

-1 risk of bias

-2 imprecision

-1 risk of bias

MBP vs. None

 

-2 imprecision

-1 risk of bias

-2 imprecision

-1 risk of bias

-2 imprecision

-1 risk of bias

 

Table 2. Relative risk plus the level of evidence per comparison for surgical site infection, anastomotic leakage, and mortality.

A systematic review of the literature was performed to answer the following question:

 

P:           Adults undergoing elective colorectal surgery.

I:            Mechanical bowel preparation (MBP), oral antibiotics alone (OA), a combination of

     oral antibiotics and mechanical bowel preparation (MBP-OA).

C:           No bowel preparation, MBP, OA, or MBP-OA.

O:          Surgical site infections (SSI), anastomotic leakage, mortality.

 

Relevant outcome measures

The guideline development group considered the occurrence of surgical site infections as a critical outcome measure for decision making; and anastomotic leakage and mortality as important outcome measures for clinical decision making.

 

The working group defined a threshold of 10% for continuous outcomes and a relative risk (RR) for dichotomous outcomes of <0.80 and >1.25 as a minimal clinically (patient) important difference.

 

Search and select (Methods)

The databases Pubmed, Medline (via OVID) and Embase (via Embase.com) were searched with relevant search terms until 10-08-2021. The detailed search strategy is depicted under the tab Methods. The systematic literature search resulted in 3040 hits, eight additional studies were found through forward and backward citation tracking. Studies were selected based on the following criteria: systematic reviews and RCTs on the question of the effect of MBP with oral antibiotics, MBP alone, and oral antibiotics alone. One hundred twenty-three studies were initially selected based on title and abstract screening. After reading the full text, 75 studies were excluded (see the exclusion table with reasons for exclusion), and 48 studies were included.

 

Results

Forty-eight studies were included in the final analysis. Important study characteristics and results are summarized in the evidence tables. The assessment of the risk of bias is summarized in the risk of bias tables.

  1. Abis GSA, Stockmann HBAC, Bonjer HJ, et al. Randomized clinical trial of selective decontamination of the digestive tract in elective colorectal cancer surgery (SELECT trial). Br J Surg. 03 2019;106(4):355-363. doi:10.1002/bjs.11117
  2. Anjum N, Ren J, Wang G, et al. A Randomized Control Trial of Preoperative Oral Antibiotics as Adjunct Therapy to Systemic Antibiotics for Preventing Surgical Site Infection in Clean Contaminated, Contaminated, and Dirty Type of Colorectal Surgeries. Dis Colon Rectum. Dec 2017;60(12):1291-1298. doi:10.1097/DCR.0000000000000927
  3. Arezzo A, Mistrangelo M, Bonino MA, et al. Oral neomycin and bacitracin are effective in preventing surgical site infections in elective colorectal surgery: a multicentre, randomized, parallel, single-blinded trial (COLORAL-1). Updates Surg. Jun 20 2021;doi:10.1007/s13304-021-01112-5
  4. Bertani E, Chiappa A, Biffi R, et al. Comparison of oral polyethylene glycol plus a large volume glycerine enema with a large volume glycerine enema alone in patients undergoing colorectal surgery for malignancy: a randomized clinical trial. Colorectal Dis. Oct 2011;13(10):e327-34. doi:10.1111/j.1463-1318.2011.02689.x
  5. Bhat AH, Parray FQ, Chowdri NA, et al. Mechanical bowel preparation versus no preparation in elective colorectal surgery: a prospective randomized study. International Journal of Surgery Open. 2016;2:26-30.
  6. Bhattacharjee PK, Chakraborty S. An Open-Label Prospective Randomized Controlled Trial of Mechanical Bowel Preparation vs Nonmechanical Bowel Preparation in Elective Colorectal Surgery: Personal Experience. Indian J Surg. Dec 2015;77(Suppl 3):1233-6. doi:10.1007/s12262-015-1262-3
  7. Bretagnol F, Panis Y, Rullier E, et al. Rectal cancer surgery with or without bowel preparation: The French GRECCAR III multicenter single-blinded randomized trial. Ann Surg. Nov 2010;252(5):863-8. doi:10.1097/SLA.0b013e3181fd8ea9
  8. Bucher P, Gervaz P, Soravia C, Mermillod B, Erne M, Morel P. Randomized clinical trial of mechanical bowel preparation versus no preparation before elective left-sided colorectal surgery. Br J Surg. Apr 2005;92(4):409-14. doi:10.1002/bjs.4900
  9. Burke P, Mealy K, Gillen P, Joyce W, Traynor O, Hyland J. Requirement for bowel preparation in colorectal surgery. Br J Surg. Jun 1994;81(6):907-10. doi:10.1002/bjs.1800810639
  10. Coppa GF, Eng K. Factors involved in antibiotic selection in elective colon and rectal surgery. Surgery. Nov 1988;104(5):853-8.
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  13. Fa-Si-Oen P, Roumen R, Buitenweg J, et al. Mechanical bowel preparation or not? Outcome of a multicenter, randomized trial in elective open colon surgery. Dis Colon Rectum. Aug 2005;48(8):1509-16. doi:10.1007/s10350-005-0068-y
  14. Güenaga KF, Matos D, Wille‐Jørgensen P. Mechanical bowel preparation for elective colorectal surgery. Cochrane database of systematic reviews. 2011(9).
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  16. Hata H, Yamaguchi T, Hasegawa S, et al. Oral and Parenteral Versus Parenteral Antibiotic Prophylaxis in Elective Laparoscopic Colorectal Surgery (JMTO PREV 07-01): A Phase 3, Multicenter, Open-label, Randomized Trial. Ann Surg. Jun 2016;263(6):1085-91. doi:10.1097/SLA.0000000000001581
  17. Horie T. Randomized controlled trial on the necessity of chemical cleaning as preoperative preparation for Colorectal Cancer Surgery. 2007;
  18. Ikeda A, Konishi T, Ueno M, et al. Randomized clinical trial of oral and intravenous versus intravenous antibiotic prophylaxis for laparoscopic colorectal resection. Br J Surg. Nov 2016;103(12):1608-1615. doi:10.1002/bjs.10281
  19. Ishida H, Yokoyama M, Nakada H, Inokuma S, Hashimoto D. Impact of oral antimicrobial prophylaxis on surgical site infection and methicillin-resistant Staphylococcus aureus infection after elective colorectal surgery. Results of a prospective randomized trial. Surgery today. 2001;31(11):979-983.
  20. Jalalzadeh H, Wolfhagen N, Harmsen WJ, Griekspoor M, Boermeester MA. A Network Meta-Analysis and GRADE Assessment of the Effect of Preoperative Oral Antibiotics with and Without Mechanical Bowel Preparation on Surgical Site Infection Rate in Colorectal Surgery. Annals of Surgery Open. 2022 Sep 1;3(3):e175.
  21. Kobayashi M, Mohri Y, Tonouchi H, et al. Randomized clinical trial comparing intravenous antimicrobial prophylaxis alone with oral and intravenous antimicrobial prophylaxis for the prevention of a surgical site infection in colorectal cancer surgery. Surg Today. 2007;37(5):383-8. doi:10.1007/s00595-006-3410-7
  22. Koskenvuo L, Lehtonen T, Koskensalo S, et al. Mechanical and oral antibiotic bowel preparation versus no bowel preparation for elective colectomy (MOBILE): a multicentre, randomised, parallel, single-blinded trial. Lancet. 09 2019;394(10201):840-848. doi:10.1016/S0140-6736(19)31269-3
  23. Lewis RT. Oral versus systemic antibiotic prophylaxis in elective colon surgery: a randomized study and meta-analysis send a message from the 1990s. Can J Surg. Jun 2002;45(3):173-80.
  24. Mai-Phan AT, Nguyen H, Nguyen TT, Nguyen DA, Thai TT. Randomized controlled trial of mechanical bowel preparation for laparoscopy-assisted colectomy. Asian J Endosc Surg. Oct 2019;12(4):408-411. doi:10.1111/ases.12671
  25. Miettinen RP, Laitinen ST, Mäkelä JT, Pääkkönen ME. Bowel preparation with oral polyethylene glycol electrolyte solution vs. no preparation in elective open colorectal surgery: prospective, randomized study. Dis Colon Rectum. May 2000;43(5):669-75; discussion 675-7. doi:10.1007/BF02235585
  26. Mulder T, Crolla RMPH, Kluytmans-van den Bergh MFQ, et al. Preoperative Oral Antibiotic Prophylaxis Reduces Surgical Site Infections After Elective Colorectal Surgery: Results From a Before-After Study. Clin Infect Dis. 2019;69(1):93-99. doi:10.1093/cid/ciy839
  27. Mulder T, Kluytmans-van den Bergh M, Vlaminckx B, et al. Prevention of severe infectious complications after colorectal surgery using oral non-absorbable antimicrobial prophylaxis: results of a multicenter randomized placebo-controlled clinical trial. Antimicrob Resist Infect Control. Jun 15 2020;9(1):84. doi:10.1186/s13756-020-00745-2
  28. National Institute for Health and Care Excellence (NICE). 2019 exceptional surveillance of surgical site infections: prevention and treatment (NICE guideline NG125)
  29. Lau WY, Chu KW, Poon GP, Ho KK. Prophylactic antibiotics in elective colorectal surgery. Br J Surg. Aug 1988;75(8):782-5. doi:10.1002/bjs.1800750819
  30. O'Hara LM, Thom KA, Preas MA. Update to the Centers for Disease Control and Prevention and the Healthcare Infection Control Practices Advisory Committee Guideline for the Prevention of Surgical Site Infection (2017): A summary, review, and strategies for implementation. Am J Infect Control. 2018;46(6):602-609. doi:10.1016/j.ajic.2018.01.018
  31. Oshima T, Takesue Y, Ikeuchi H, et al. Preoperative oral antibiotics and intravenous antimicrobial prophylaxis reduce the incidence of surgical site infections in patients with ulcerative colitis undergoing IPAA. Dis Colon Rectum. Oct 2013;56(10):1149-55. doi:10.1097/DCR.0b013e31829f71a0
  32. Papp G, Saftics G, Szabó BE, et al. Systemic versus Oral and Systemic Antibiotic Prophylaxis (SOAP) study in colorectal surgery: prospective randomized multicentre trial. Br J Surg. Apr 2021;108(3):271-276. doi:10.1093/bjs/znaa131
  33. Pena-Soria MJ, Mayol JM, Anula R, Arbeo-Escolar A, Fernandez-Represa JA. Single-blinded randomized trial of mechanical bowel preparation for colon surgery with primary intraperitoneal anastomosis. J Gastrointest Surg. Dec 2008;12(12):2103-8; discussion 2108-9. doi:10.1007/s11605-008-0706-5
  34. Platell C, Barwood N, Makin G. Randomized clinical trial of bowel preparation with a single phosphate enema or polyethylene glycol before elective colorectal surgery. Br J Surg. Apr 2006;93(4):427-33. doi:10.1002/bjs.5274
  35. Playforth MJ, Smith GM, Evans M, Pollock AV. Antimicrobial bowel preparation. Oral, parenteral, or both? Dis Colon Rectum. Feb 1988;31(2):90-3. doi:10.1007/BF02562635
  36. Ram E, Sherman Y, Weil R, Vishne T, Kravarusic D, Dreznik Z. Is mechanical bowel preparation mandatory for elective colon surgery? A prospective randomized study. Arch Surg. Mar 2005;140(3):285-8. doi:10.1001/archsurg.140.3.285
  37. Reynolds J, Jones J, Evans D, Hardcastle J. Do preoperative oral antibiotics influence sepsis rates following elective colorectal surgery in patients receiving perioperative intravenous prophylaxis. Surg Res Commun. 1989;7:71-77.
  38. Rollins KE, Javanmard-Emamghissi H, Acheson AG, Lobo DN. The Role of Oral Antibiotic Preparation in Elective Colorectal Surgery: A Meta-analysis. Ann Surg. 2019;270(1):43-58. doi:10.1097/SLA.0000000000003145
  39. Roos D, Dijksman LM, Oudemans-van Straaten HM, de Wit LT, Gouma DJ, Gerhards MF. Randomized clinical trial of perioperative selective decontamination of the digestive tract versus placebo in elective gastrointestinal surgery. Br J Surg. Oct 2011;98(10):1365-72. doi:10.1002/bjs.7631
  40. Rybakov E, Nagudov M, Sukhina M, Shelygin Y. Impact of oral antibiotic prophylaxis on surgical site infection after rectal surgery: results of randomized trial. Int J Colorectal Dis. Feb 2021;36(2):323-330. doi:10.1007/s00384-020-03746-0
  41. Sadahiro S, Suzuki T, Tanaka A, et al. Comparison between oral antibiotics and probiotics as bowel preparation for elective colon cancer surgery to prevent infection: prospective randomized trial. Surgery. Mar 2014;155(3):493-503. doi:10.1016/j.surg.2013.06.002
  42. Sasaki J, Matsumoto S, Kan H, et al. Objective assessment of postoperative gastrointestinal motility in elective colonic resection using a radiopaque marker provides an evidence for the abandonment of preoperative mechanical bowel preparation. J Nippon Med Sch. 2012;79(4):259-66. doi:10.1272/jnms.79.259Schardey HM,
  43. Stellato TA, Danziger LH, Gordon N, et al. Antibiotics in elective colon surgery. A randomized trial of oral, systemic, and oral/systemic antibiotics for prophylaxis. Am Surg. Apr 1990;56(4):251-4.
  44. Suzuki T, Sadahiro S, Tanaka A, et al. Usefulness of Preoperative Mechanical Bowel Preparation in Patients with Colon Cancer who Undergo Elective Surgery: A Prospective Randomized Trial Using Oral Antibiotics. Dig Surg. 2020;37(3):192-198. doi:10.1159/000500020
  45. Takesue Y, Yokoyama T, Akagi S, et al. A brief course of colon preparation with oral antibiotics. Surg Today. 2000;30(2):112-6. doi:10.1007/PL00010059
  46. Taylor EW, Lindsay G. Selective decontamination of the colon before elective colorectal surgery. West of Scotland Surgical Infection Study Group. World J Surg. 1994 Nov-Dec 1994;18(6):926-31; discussion 931-2. doi:10.1007/BF00299111
  47. Toh JWT, Phan K, Hitos K, et al. Association of Mechanical Bowel Preparation and Oral Antibiotics Before Elective Colorectal Surgery With Surgical Site Infection: A Network Meta-analysis. JAMA Netw Open. 2018;1(6):e183226. Published 2018 Oct 5. doi:10.1001/jamanetworkopen.2018.3226
  48. Uchino M, Ikeuchi H, Bando T, et al. Efficacy of Preoperative Oral Antibiotic Prophylaxis for the Prevention of Surgical Site Infections in Patients With Crohn Disease: A Randomized Controlled Trial. Ann Surg. 03 2019;269(3):420-426. doi:10.1097/SLA.0000000000002567
  49. Viddal KO, Semb LS. Tinidazole and doxycycline compared to doxycycline alone as prophylactic antimicrobial agents in elective colorectal surgery. Scand J Gastroenterol Suppl. 1980;59:21-4.
  50. Watanabe M, Murakami M, Nakao K, Asahara T, Nomoto K, Tsunoda A. Randomized clinical trial of the influence of mechanical bowel preparation on faecal microflora in patients undergoing colonic cancer resection. Br J Surg. Dec 2010;97(12):1791-7. doi:10.1002/bjs.7253
  51. Woodfield JC, Clifford K, Schmidt B, Turner GA, Amer MA, McCall JL. Strategies for Antibiotic Administration for Bowel Preparation Among Patients Undergoing Elective Colorectal Surgery: A Network Meta-analysis. JAMA Surg. 2022;157(1):34-41. doi:10.1001/jamasurg.2021.5251
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  53. Zmora O, Mahajna A, Bar-Zakai B, et al. Colon and rectal surgery without mechanical bowel preparation: a randomized prospective trial. Ann Surg. Mar 2003;237(3):363-7. doi:10.1097/01.SLA.0000055222.90581.59

Evidence tables

 

MBP vs MBP-OA: 23 RCTs

Study

SSI*/ N total

N – T1

N -

T2

Type of surgery

Open / laparoscopic

MBP regimen

OA regimen

Preoperative IV SAP and intraoperateive redosing

 

Papp

2021 1

52 / 529

276

253

Colorectal surgery with anastomosis (excl loop CC)

Mixed

40ml castor oil + 20ml paraffin

day before surgery + enema day before and morning of surgery

Metronidazole 500mg + neomycin sulphate 1g

day before surgery (13h, 15h, 19h)

Ceftriaxone 2g + metronidazole 500mg,

Redose > 4hrs and/or blood loss > 1500ml

 

Rybakov

2020 2

17 / 116

57

59

(L)AR, APR, intersphincteric resection

Mixed

PEG

day before surgery (16h)

Erythromycin 500mg + metronidazole 500mg

day before surgery (17h, 20h, 23h)

Ceftriaxone 1000mg

 

Schardey 2020 3

15 / 80

40

40

(L)AR

Mixed

PEG + electrolytes 3-6L

day before surgery

Polymyxin B 100 mg + tobramycin 80 mg + vancomycin 125 mg,

day before surgery till day 7, 4 times daily

Decided by surgeon

 

Abis

2019 4

65 / 455

227

228

LAR, LH, RH, TH, SR, other

Mixed

Unknown kind

* Only patients undergoing left-sided colonic, sigmoid and LAR

Amphotericin B 500 mg + 5 colistin sulphate 100 mg + tobramycin 80 mg,

3 days before till minimum of 3 days after surgery, 4 times daily

Cefazolin 1g + metronidazole 500 mg,

Redose > 4hrs

 

Uchino

2019 5

63 / 325

162

163

Intestinal resection

(Small bowel resections included

Open

Sodium picosulphate hydrate 20ml 0.75%

Kanamycin 500mg + metronidazole 500mg

day before surgery (14h, 15, 21h)

Flomoxef

Redose every 3 hrs

 

Anjum

2017 6

34 / 184

93

91

LAR, LH, RH

Mixed

Sodium phosphate 133ml twice

day before surgery

Metronidazole 400 mg + levofloxacin 200 mg

day before surgery (15h, 19h, 23h)

Cephalosporin (2nd gen) + metronidazole,

Redose every 3 hrs

 

Hata

2016 7

58 / 579

290

289

AR, APR, colectomy

laparoscopic

Sodium picosulphate 75mg + magnesium citrate 34 g + water 180ml, day before surgery

Metronidazole 750mg + kanamycin 1g

13hrs and 9hrs before surgery

Cefmetazole 1g,

Redose every 3 hrs

 

Ikeda

2016 8

51 / 511

256

255

AR, APR, colonic surgery

laparoscopic

Magnesium citrate + sodium picosulphate

day before surgery (8h + 11h)

Metronidazole 750mg + kanamycin 1g

day before surgery (15h, 21h)

Cefmetazole,

Redose >3hrs

 

Sadahiro 2014 9

38 / 194

99

95

Resection of colorectal tumor

Mixed

Sodium picosulphate 10ml 2 days before surgery + PEG 2.000ml day before surgery (morning)

Kanamycin 500mg + metronidazole 500mg

day before surgery (13h, 14h, 23h)

Flomoxef 1g,

Redsose >3hrs

 

Oshima

2013 10

28 / 195

98

97

Proctocolectomy

Open

Magnesium citrate solution 1.8L

day before surgery (11h)

Kanamycin 500mg + metronidazole 500mg

day before surgery  (14h, 15h, 21h)

Flomoxef 1g,

Redose >3hrs

 

Roos

2011 11

60 / 289

146

143

LH, RH, TH, (L)AR, ICR, SR, PC, CC, hepatopan-creatobiliary surgery, esophageal /gastric resection, other

Mixed

PEG + electrolytes or sodium picosulphate

Polymixin B sulphate 100mg + tobramycin 80mg + amphotericin B 500mg

Cefuroxime 1.5g + metronidazole 500mg

 

Horie

2007 12

26 / 91

45

46

Resection of colorectal tumor

Open

PEG 2L

16hrs before surgery

Kanamycin 1500mg daily

start 3 days before surgery

Cefotiam hydrochloride

 

Kobayashi

2007 13

43 / 484

242

242

AR, APR, anoabdomino -rectal resection, Hartmann’s procedure

N/A

PEG 2L

day before surgery (10h)

Kanamycin 1g + erythromycin 400mg

day before surgery (14h, 15h, 23 h)

Cefmetazole 1g after,

Redose >3hrs

 

Espin Basany

2005 14

32 / 300

100

200

AR, APR, SR, segmental colon resection, TME-coloanal

Open

Sodium phosphate oral solution 45ml diluted in 90 ml of water

day before surgery (11h, 17h)

Neomycin 1g + metronidazole 1g

day before surgery (15h, 19h, 23h) OR

Neomycin 1g + metronidazole 1g

day before surgery (15h)

Cefoxitin 1g

 

Lewis

2002 15

27 / 208

104

106

AR, APR, LH, RH, TH

N/A

Sodium phosphate until clear rectal effluent. If required, additional saline enemas day before surgery (18h)

Neomycin 2g + metronidazole 2g

day before surgery (19h, 23h)

Amikacin 1g + metronidazole 1g

 

Ishida

2001 16

45 / 143

71

72

AR, APR, PC, colectomy, total pelvic exenteration, other

N/A

PEG 2L

day before surgery (15h-19h)

Kanamycin 500mg + erythromycin 400mg, start 2 days before surgery, 4 times daily

Cefotiam 1g

 

Takesue

2000 17

16 / 83

45

38

LAR, APR, LH, RH, TH, SR, ICR

N/A

PEG

day before surgery (10h-14h)

Kanamycin 500mg + metronidazole 500mg

day before surgery (14h, 15h, 23h)

Cefmetazole 1g

 

Taylor

1994 18

83 / 368

189

179

APR, colo(rectal) resection, Hartmann’s resection, other

N/A

Sodium picosulphate 1 sachets, day before surgery twice daily

Ciprofloxacin 500mg, 2 doses

day before surgery

Piperacillin 4g

 

Stellato

1990 19

10 / 102

51

51

(Colo)rectal resection

N/A

Magnesium citrate 1.745 g in 296ml (morning) + (bi)phosphate enema 118ml (evening)

day before and day of surgery

Neomycin 1g + erythromycin 1g

day before surgery (11h, 14h, 23h)

Cefoxitin 2g

 

Reynolds

1989 20

35 / 400

104

107

(Colo)rectal resection

N/A

Magnesium sulphate 4g (up to 8 times) start 3 days before surgery + sodium picosulphate twice on day before surgery

Metronidazole 500mg (3 times daily) + neomycin 1g

start day before surgery, 4 times daily

Piperacillin 2g

 

Coppa

1988 21

35 / 310

141

169

(Colo)rectal resection

N/A

Sodium phosphate

day 2 and 3 before surgery + saline enemas two days before surgery

Neomycin 8g/day, including loading dose + erythromycin 4g/day

in doses for 24hrs before surgery

Cefoxitin 1-2g

(weight adjusted)

 

Lau

1988 22

16 / 132

67

65

(L)AR, APR, LH, RH, TH, SR, subtotal colectomy, pelvic exenteration, palliative bypass

Open

Bisacodyl and magnesium sulphate + saline enemas

Neomycin 1g + erythromycin 1g

day before surgery (13h, 14h, 23h)

Metronidazole 500mg + gentamicin 2mg/kg

 

Playforth 1988 23

36 / 119

58

61

(Colo)rectal resection

N/A

Mannitol 100g in 1L water

day before operation

Neomycin 1g every six hrs + metronidazole 200mg every four hrs

start 24hrs before surgery

 

Metronidazole 0.5g

 

 

MBP vs no preparation: 16 RCTs

Mai-Phan 2019 24

21 / 122

62

60

Colectomy

Laparoscopic

Sodium phosphate 2 bottles or PEG 2L

 

Yes, unknown kind

 

Bhat

2016 25

28 / 202

98

104

(L)AR, APR, LH, RH, TH, SR

N/A

PEG 2 packs in 4L water

12–16hrs before surgery

 

Ceftriaxone 1g + metronidazole 500mg

 

Bhattacharjee 2015 26

27 / 71

38

33

LAR, APR, LH, RH, SR, PC

Open

PEG 1 pack in 2L water

afternoon before surgery

 

Cefuroxime 1.5g + metronidazole 500 mg,

 

Sasaki

2012 27

6 / 79

38

41

LH, RH

Mixed

Sodium picosulphate hydrate 10mL start evening 2 days before surgery + 2L PEG morning before surgery

 

Flomoxef 1g,

Redose >3hrs

 

Bertani
2011 28

42 / 229

114

115

LAR, LH, RH, TH, 

Mixed

PEG 70mg in 1L, day before surgery four times (16h-20h) + glycerin enema 5% 2L day of surgery

 

Cefoxitin 2g (allergy: gentamicin 80mg + clindamycin 600mg or metronidazole 500mg)

 

Bretagnol 2010 29

34 / 178

89

89

Rectal cancer sphincter saving resection

Mixed

Senna solution 1-2 packs in water 24h before surgery + povidone-iodine enema 1L evening before and >2h before surgery

 

Ceftriaxone 1g + metronidazole 500mg,

Redose >2hrs

 

Watanabe 2010 30

3 / 42

21

21

Colonic resection

Mixed

Magnesium citrate 1.8L, 16–19h before surgery + glycerin enema 120mL, day of surgery

 

Cefmetazole,

Redose every 3hrs

 

Pena-Soria 2008 31

37 / 129

65

64

Colon or proximal rectal resection

Open

PEG 3L + conventional enemas

 

Gentamicin 80mg + metronidazole 500mg

 

Contant

2007 32

283 / 1354

670

684

Colorectal surgery with anastomosis

Open

PEG 2-4L + bisacodyl or sodium phosphate solution 

 

Local guideline

 

Jung

2007 33

142 / 1343

686

657

Surgery of the colon with anastomosis

Open

PEG, sodium phosphate

Some patients only received enema

 

Local guideline

 

Platell

2006 34

52 / 294

147

147

AR, RH, TH, PC, (sub)total colectomy

Open

PEG 3L

day before surgery

Sodium phosphate enema,

2-4hrs before surgery

Ticarcillin disodium / clavulanate potassium 3.1 g or gentamicin 2mg/kg + metronidazole 500mg

 

Bucher 2005 35

23 / 153

78

75

AR, LH, TH, closure of Hartmann’s

Mixed

PEG 3L, 12-16hrs before surgery + saline enema 250ml before AR

Saline enema 250 mL when AR

Metronidazole + ceftriaxone

 

Fa-Si-Oen 2005 36

29 / 250

125

125

LH, RH, TH, SR, other

Open

PEG 4L

 

Cefazolin 2g + metronidazole 1.5g or gentamicin 240mg + metronidazole 1.5g

 

Ram

2005 37

38 / 329

164

165

(L)AR, APR, , LH, RH, TH, SR, subtotal colectomy

Open

Sodium phosphate

day before surgery

 

Metronidazole 500mg + ceftriaxone 1g

 

Miettinen 2000 38

23 / 267

138

129

(L)AR, APR, LH, RH, CC, ileal pouch

Open

PEG until clear fluid

day before surgery

 

Ceftriaxone 2g + metronidazole 1g

 

Burke

1994 39

14 / 169

82

87

AR, LH

N/A

Sodium picosulphate 10mg, day before surgery (morning, afternoon)

 

Ceftriaxone 1g + metronidazole 500mg

 

 

OA vs None: 5 RCTs

Arezzo 2021 40

34/204

100

104

RH, ICR, TH, LH, AR, subtotal colectomy, Hartmann procedure, other

Mixed

* Some patients undergoing left sided colonic and anterior resections received MBP according to local guidelines

Neomycin 25.000 UI (≈ 33mg) + bacitracin 2500 UI (≈ ,33mg)

(24h, 16h + 8h before surgery)

Amoxicillin 2g + clavulanic acid 200mg (allergy:  clindamycin 600mg + gentamycin 2mg/kg)

Redosing if prolonged surgery

 

Espin Basany 2020 41

193 / 536

267

269

LH, RH, colectomy, segment resection, other

Mixed

 

Ciprofloxacin 750mg

day before surgery (12h, midnight) + metronidazole 250mg

day before surgery (12h, 18h, midnight)

Cefuroxime 5g + metronidazole 1g

 

Mulder

2020 42

11 / 78

39

39

LAR, LH, RH, SR, (sub) total colectomy, other

Mixed

 

Tobramycin 80mg + colistin sulphate 100mg

start 3 days before surgery 4 times daily

According to national guideline

 

Hanel

1980 43

0 / 67

34

33

(Colo)rectal resection

N/A

Daily enemas, start 4 days before surgery

Metronidazole 200mg

start four days before surgery 4 times daily  + neomycin 1g

start two day before surgery twice daily

+ daily enemas, start 4 days before surgery

Clindamycin 7mg/kg + cefazolin sodium 1g

 

Viddal

1980 44

2 / 42

21

21

LAR, LH, RH, APR, PC, CC, jejunoileostomy, ileotransversostomy

Open

Enemas for 3 days before surgery

Tinidazole 2g

start day before surgery and day 3-5 postoperatively

+ enemas for 3 days before surgery

Doxycycline 200mg

 

 

OA vs MBP-OA: 3 RCTs

Suzuki 2020 45

15 / 251

126

125

Colectomy

Mixed

Sodium picosulphate 10mL,

2 days before surgery +

PEG 2L, morning before surgery

Kanamycin sulfate 500mg + metronidazole 500mg

day before surgery (13h, 14h, 23h)

Flomoxef 1g,

Redose >3hrs

 

Zmora 2006 46

32 / 249

129

120

(L)AR, LH, SR, closure of Hartmann’s

N/A

PEG 1 gallon

day before surgery

+ sodium (bi)phosphate enema day of rectal surgery

Neomycin 1g + erythromycin 1g

day before surgery, 3 doses

+ sodium (bi)phosphate enema day of rectal surgery

Metronidazole 500mg + gentamicin 240 mg + ampicillin 1g

 

Zmora 2003 47

36 / 380

193

187

AR, LH, RH, SR, APR closure of Hartmann’s

N/A

PEG 1 gallon

12hrs-16hrs before surgery

+ sodium (bi)phosphate enema day of rectal surgery

Neomycin + erythromycin, 3 doses (unknown dose and timing)

+ sodium (bi)phosphate enema day of rectal surgery

Broad spectrum

 

 

MBP-OA vs None: 1 RCT

Koskenvuo 2019 48

34 / 397

196

200

LH, RH, TH, AR, ICR, SR, subtotal colectomy, other

Mixed

PEG 2L + 1L clear fluid

day before surgery

Neomycin 2g (19h) + metronidazole 2g (23h)

day before surgery

Cefuroxime 1500 mg + metronidazole 500 mg,

Redose >3hrs and/or blood loss >1,5L

 

 

APR: abdominoperineal resection, CC: colostoma closure, ICR: ileocecal resection, (L)AR: (low) anterior resection, LH: left hemicolectomy, N/A: not available PC: proctocolectomy, PEG: polyethylene glycol, RH: right hemicolectomy, SG: sigmoid resection, TH: transverse hemicolectomy, TME: total mesorectal excision. * Anastomotic leakage included in SSI

 

Risk of bias assessment

 

 

Funnel plots

6.a. Total SSI

 

6.b. Anastomotic leakage

6.c. Mortality

Table of excluded studies

 

Author, Year

Reason for exclusion

1.

Apte 2020

Study protocol

2.

Vadwana 2020

No RCT

3.

Mulder 2018

Study protocol

4.

Vignaud 2018

Study protocol

5.

Hu 2018

Language outside scope

6.

Kobayashi 2015

Language outside scope

7.

Beerdawood 2014

Emergency surgeries included

8.

Collin 2014

Irrelevant outcome or comparison

9.

Saha 2014

Emergency surgeries included

10.

Dijksman 2012

Irrelevant outcome or comparison

11.

Kolovrat 2012

No RCT

12.

Scabini 2012

Retracted

13.

Van’t Sant 2012

Subanalysis of Contant 2007

14.

Khan 2011

Not retrievable

15.

Roig 2011

No RCT

16.

Van’t Sant 2011

Subanalysis of Contant 2007

17

Scabini 2010

Retracted

18.

Van’t Sant 2010

Subanalysis of Contant 2007

19.

Gravante 2009

Comment or letter

20.

Roos 2009

No RCT

21.

Alcantara Moral 2009

Language outside scope

22.

Takesue 2009

Poster presentation

23.

Leiro 2008

Language outside scope

24.

Itani 2007

Irrelevant outcome or comparison

25.

Pena-Soria 2007

Interim analysis Pena-Soria 2008

26.

Platell 2007

Comment or letter

27.

Reddy 2007

No preoperative iv SAP

28.

Verma 2007

Not retrievable

29.

Bucher 2006

Irrelevant outcome or comparison

30.

Bucher 2006

Erratum

31.

Fa-Si-Oen 2005

Irrelevant outcome or comparison

32.

Gray 2005

No RCT

33.

Van Geldere 2002

No RCT

34.

Young Tabusso 2002

Language outside scope

35.

Fillmann 2001

Not retrievable 

36.

Kale 1998

Irrelevant outcome or comparison

37.

Torres Panuncia 1998

Not retrievable 

38.

Yabata 1997

No preoperative iv SAP 

39.

Fillman 1995

Language outside scope

40.

Santos Jr 1994

Children included

41.

Tan 1993

Not retrievable 

42.

Brownson 1992

Abstract only

43.

Tsimoyiannis 1991

Irrelevant outcome or comparison

44.

Gardini 1990

Language outside of scope

45.

Nohr 1990

Not retrievable 

46.

Vacher 1990

Language outside of scope

47.

Cann 1988

Irrelevant outcome or comparison

48.

Gruttadauria 1987

Not retrievable 

49.

Peruzzo 1987

Not retrievable 

50.

Gottrup 1985

No preoperative iv SAP

51.

Sgarlato 1984

Irrelevant outcome or comparison

52.

Hinchey 1983

Irrelevant outcome or comparison

53.

May 1983

No RCT

54.

Gerritsen 1982

No preoperative iv SAP

55.

Keighley 1982

Irrelevant outcome or comparison

56.

Lazorthes 1982

No preoperative iv SAP

57.

Burdon 1981

Not retrievable 

58.

Goldring 1981

Not retrievable 

59.

Lewis 1981

No preoperative iv SAP

60.

Barber 1979

Not retrievable 

61.

Condon 1979

No preoperative iv SAP

62.

Molin 1979

Not retrievable 

63.

Montariol 1979

Language outside scope

64.

Wapnick 1979

No preoperative iv SAP

65.

Brogden 1978

No RCT

66.

Gillespie 1978

No preoperative iv SAP

67.

Hojer 1978

No preoperative iv SAP

68.

Matheson 1978

No preoperative iv SAP

69.

Vargish 1978

No preoperative iv SAP

70.

Clarke 1977

No preoperative iv SAP

71.

Mendes da Costa 1977

Not retrievable 

72.

Nichols 1977

Irrelevant outcome or comparison

73.

Semb 1977

Abstract only

74.

Schneiders 1977

No preoperative iv SAP

75.

Wetterfors 1976

No preoperative iv SAP

76.

Goldring 1975

No preoperative iv SAP

77.

Nichols 1973

No preoperative iv SAP

78.

Barker 1971

No preoperative iv SAP

79.

Hulbert 1967

No preoperative iv SAP

 

*SAP = surgical antimicrobial prophylaxis

 

Autorisatiedatum en geldigheid

Laatst beoordeeld  : 01-12-2024

Laatst geautoriseerd  : 01-12-2024

Geplande herbeoordeling  : 01-12-2026

Initiatief en autorisatie

Initiatief:
  • Nederlandse Vereniging voor Heelkunde
  • Samenwerkingsverband Richtlijnen Infectiepreventie
Geautoriseerd door:
  • Nederlands Oogheelkundig Gezelschap
  • Nederlandse Internisten Vereniging
  • Nederlandse Orthopaedische Vereniging
  • Nederlandse Vereniging voor Anesthesiologie
  • Nederlandse Vereniging voor Dermatologie en Venereologie
  • Nederlandse Vereniging voor Heelkunde
  • Nederlandse Vereniging voor Keel-Neus-Oorheelkunde en Heelkunde van het Hoofd-Halsgebied
  • Nederlandse Vereniging voor Kindergeneeskunde
  • Nederlandse Vereniging voor Medische Microbiologie
  • Nederlandse Vereniging voor Neurochirurgie
  • Nederlandse Vereniging voor Obstetrie en Gynaecologie
  • Nederlandse Vereniging voor Plastische Chirurgie
  • Nederlandse Vereniging voor Thoraxchirurgie
  • Verpleegkundigen en Verzorgenden Nederland
  • Vereniging voor Hygiëne en Infectiepreventie in de Gezondheidszorg
  • Patiëntenfederatie Nederland
  • Landelijke Vereniging van Operatieassistenten
  • Nederlandse Vereniging van Anesthesiemedewerkers

Algemene gegevens

De ontwikkeling/herziening van deze richtlijnmodule werd ondersteund door het Kennisinstituut van de Federatie Medisch Specialisten (www.demedischspecialist.nl/kennisinstituut) en werd gefinancierd uit de Kwaliteitsgelden Medisch Specialisten (SKMS). De financier heeft geen enkele invloed gehad op de inhoud van de richtlijnmodule.

Samenstelling werkgroep

Voor het ontwikkelen van de richtlijnmodules 2 tot 16 is in 2020 op initiatief van de NVvH een multidisciplinaire werkgroep ingesteld, bestaande uit vertegenwoordigers van alle relevante specialismen (zie hiervoor de Samenstelling van de werkgroep) die betrokken zijn bij de zorg voor preventie van postoperatieve wondinfecties. Daarnaast is in 2022 op initiatief van het Samenwerkingsverband Richtlijnen Infectiepreventie (SRI) een separate multidisciplinaire werkgroep samengesteld voor de herziening van de WIP-richtlijn over postoperatieve wondinfecties: module 17-22. De ontwikkelde modules van beide werkgroepen zijn in deze richtlijn samengevoegd.

Belangenverklaringen

De Code ter voorkoming van oneigenlijke beïnvloeding door belangenverstrengeling is gevolgd. Alle werkgroepleden hebben schriftelijk verklaard of zij in de laatste drie jaar directe financiële belangen (betrekking bij een commercieel bedrijf, persoonlijke financiële belangen, onderzoek financiering) of indirecte belangen (persoonlijke relaties, reputatiemanagement) hebben gehad. Gedurende de ontwikkeling of herziening van een module worden wijzigingen in belangen aan de voorzitter doorgegeven. De belangenverklaring wordt opnieuw bevestigd tijdens de commentaarfase.

Een overzicht van de belangen van werkgroepleden en het oordeel over het omgaan met eventuele belangen vindt u in onderstaande tabel. De ondertekende belangenverklaringen zijn op te vragen bij het secretariaat van het Kennisinstituut van de Federatie Medisch Specialisten.

 

Werkgroeplid

Functie

Nevenfuncties

Gemelde belangen

Ondernomen actie

Mevr. prof. dr. M.A. Boermeester

Chirurg

* Medisch Ethische Commissie, Amsterdam UMC, locatie AMC

* Antibiotica Commissie, Amsterdam UMC

Persoonlijke financiële belangen

Hieronder staan de beroepsmatige relaties met bedrijfsleven vermeld waarbij eventuele financiële belangen via de AMC Research B.V. lopen, dus institutionele en geen persoonlijke gelden zijn: Skillslab instructeur en/of spreker (consultant) voor KCI/3M, Smith&Nephew, Johnson&Johnson, Gore, BD/Bard, TELABio, GDM, Medtronic, Molnlycke.

 

Persoonlijke relaties

Geen.

 

Extern gefinancierd onderzoek

Institutionele grants van KCI/3M, Johnson&Johnson en New Compliance.

 

Intellectuele belangen en reputatie

Ik maak me sterk voor een 100% evidence-based benadering van maken van aanbevelingen, volledig transparant en reproduceerbaar. Dat is mijn enige belang in deze, geen persoonlijk gewin.

 

Overige belangen

Geen.

 

Extra kritische commentaarronde.

Dhr. dr. M.J. van der Laan

Vaatchirurg

Vice voorzitter Consortium Kwaliteit van Zorg NFU, onbetaald

 

Persoonlijke financiële belangen

Geen.

 

Persoonlijke relaties

Geen.

 

Extern gefinancierd onderzoek

Geen.

 

Intellectuele belangen en reputatie

Geen.

 

Overige belangen

Geen.

 

Geen.

 

Dhr. dr. W.C. van der Zwet

Arts-microbioloog

Lid Regionaal Coördinatie Team, Limburgs infectiepreventie & ABR Zorgnetwerk (onbetaald)

Dhr. dr. D.R. Buis

Neurochirurg

Lid Hoofdredactieraad Tijdschrift voor Neurologie & Neurochirurgie - onbetaald

Dhr. dr. J.H.M. Goosen

Orthopaedisch Chirurg

Inhoudelijke presentaties voor Smith&Nephew en Zimmer Biomet. Deze worden vergoed per uur.

Mw. drs. H. Jalalzadeh

Arts-onderzoeker

Geen.

Persoonlijke financiële belangen

Geen.

 

Persoonlijke relaties

Geen.

 

Extern gefinancierd onderzoek

Geen.

 

Intellectuele belangen en reputatie

Geen.

 

Overige belangen

Geen.

Geen.

 

Dhr. dr. N. Wolfhagen

AIOS chirurgie

Mw. drs. H.  Groenen

Arts-onderzoeker

Dhr. dr. F.F.A. Ijpma

Traumachirurg

Dhr. dr. P. Segers

Cardiothoracaal chirurg

Mw. Y.E.M. Dreissen

AIOS neurochirurgie

Dhr. R.R. Schaad

Anesthesioloog

 

Inbreng patiëntenperspectief

Er werd aandacht besteed aan het patiëntenperspectief door uitnodigen van de Patiëntenfederatie Nederland voor de invitational conference. De verkregen input is meegenomen bij het opstellen van de uitgangsvragen, de keuze voor de uitkomstmaten en bij het opstellen van de overwegingen. De conceptmodules zijn tevens voor commentaar voorgelegd aan de Patiëntenfederatie Nederland en de eventueel aangeleverde commentaren zijn bekeken en verwerkt. Voor de modules 17-22 was de patiëntfederatie vertegenwoordigd in de werkgroep.

 

Wkkgz & Kwalitatieve raming van mogelijke substantiële financiële gevolgen

Bij de richtlijn is conform de Wet kwaliteit, klachten en geschillen zorg (Wkkgz) een kwalitatieve raming uitgevoerd of de aanbevelingen mogelijk leiden tot substantiële financiële gevolgen. Bij het uitvoeren van deze beoordeling zijn richtlijnmodules op verschillende domeinen getoetst (zie het stroomschema op de Richtlijnendatabase).

 

Uit de kwalitatieve raming blijkt dat er waarschijnlijk geen substantiële financiële gevolgen zijn.

 

Voor module 8 (Negatieve druktherapie) geldt dat uit de toetsing volgt dat de aanbeveling(en) breed toepasbaar zijn (5.000 - 40.000 patiënten). Tevens volgt uit de toetsing dat het geen nieuwe manier van zorgverlening of andere organisatie van zorgverlening betreft. Er worden daarom geen substantiële financiële gevolgen verwacht.

 

Voor de overige modules en aanbevelingen geldt dat uit de toetsing volgt dat de aanbeveling(en) breed toepasbaar zijn (>40.000 patiënten). Tevens volgt uit de toetsing dat het overgrote deel (±90%) van de zorgaanbieders en zorgverleners al aan de norm voldoet en het geen nieuwe manier van zorgverlening of andere organisatie van zorgverlening betreft. Ook wordt geen toename in het aantal in te zetten voltijdsequivalenten aan zorgverleners verwacht of een wijziging in het opleidingsniveau van zorgpersoneel. Er worden daarom geen substantiële financiële gevolgen verwacht.

Methode ontwikkeling

Evidence based

Implementatie

Zie voor de implementatie het implementatieplan in het tabblad 'Bijlagen'. 

Werkwijze

AGREE

Deze richtlijnmodule is opgesteld conform de eisen vermeld in het rapport Medisch Specialistische Richtlijnen 2.0 van de adviescommissie Richtlijnen van de Raad Kwaliteit. Dit rapport is gebaseerd op het AGREE II instrument (Appraisal of Guidelines for Research & Evaluation II; Brouwers, 2010).

 

Knelpuntenanalyse en uitgangsvragen

Tijdens de voorbereidende fase inventariseerde de werkgroepen de knelpunten in de zorg voor patiënten die chirurgie ondergaan. Tevens zijn er knelpunten aangedragen door middel van een invitational conference. De verslagen hiervan zijn opgenomen onder aanverwante producten.

Op basis van de uitkomsten van de knelpuntenanalyse zijn door de werkgroep concept-uitgangsvragen opgesteld en definitief vastgesteld.

 

Uitkomstmaten

Na het opstellen van de zoekvraag behorende bij de uitgangsvraag inventariseerde de werkgroep welke uitkomstmaten voor de patiënt relevant zijn, waarbij zowel naar gewenste als ongewenste effecten werd gekeken. Hierbij werd een maximum van acht uitkomstmaten gehanteerd. De werkgroep waardeerde deze uitkomstmaten volgens hun relatieve belang bij de besluitvorming rondom aanbevelingen, als cruciaal (kritiek voor de besluitvorming), belangrijk (maar niet cruciaal) en onbelangrijk. Tevens definieerde de werkgroep tenminste voor de cruciale uitkomstmaten welke verschillen zij klinisch (patiënt) relevant vonden.

 

Methode literatuursamenvatting

Een uitgebreide beschrijving van de strategie voor zoeken en selecteren van literatuur is te vinden onder ‘Zoeken en selecteren’ onder Onderbouwing. Indien mogelijk werd de data uit verschillende studies gepoold in een random-effects model. De beoordeling van de kracht van het wetenschappelijke bewijs wordt hieronder toegelicht.

 

Beoordelen van de kracht van het wetenschappelijke bewijs

De kracht van het wetenschappelijke bewijs werd bepaald volgens de GRADE-methode. GRADE staat voor ‘Grading Recommendations Assessment, Development and Evaluation’ (zie http://www.gradeworkinggroup.org/). De basisprincipes van de GRADE-methodiek zijn: het benoemen en prioriteren van de klinisch (patiënt) relevante uitkomstmaten, een systematische review per uitkomstmaat, en een beoordeling van de bewijskracht per uitkomstmaat op basis van de acht GRADE-domeinen (domeinen voor downgraden: risk of bias, inconsistentie, indirectheid, imprecisie, en publicatiebias; domeinen voor upgraden: dosis-effect relatie, groot effect, en residuele plausibele confounding).

GRADE onderscheidt vier gradaties voor de kwaliteit van het wetenschappelijk bewijs: hoog, redelijk, laag en zeer laag. Deze gradaties verwijzen naar de mate van zekerheid die er bestaat over de literatuurconclusie, in het bijzonder de mate van zekerheid dat de literatuurconclusie de aanbeveling adequaat ondersteunt (Schünemann, 2013; Hultcrantz, 2017).

 

GRADE

Definitie

Hoog

  • er is hoge zekerheid dat het ware effect van behandeling dichtbij het geschatte effect van behandeling ligt;
  • het is zeer onwaarschijnlijk dat de literatuurconclusie klinisch relevant verandert wanneer er resultaten van nieuw grootschalig onderzoek aan de literatuuranalyse worden toegevoegd.

Redelijk

  • er is redelijke zekerheid dat het ware effect van behandeling dichtbij het geschatte effect van behandeling ligt;
  • het is mogelijk dat de conclusie klinisch relevant verandert wanneer er resultaten van nieuw grootschalig onderzoek aan de literatuuranalyse worden toegevoegd.

Laag

  • er is lage zekerheid dat het ware effect van behandeling dichtbij het geschatte effect van behandeling ligt;
  • er is een reële kans dat de conclusie klinisch relevant verandert wanneer er resultaten van nieuw grootschalig onderzoek aan de literatuuranalyse worden toegevoegd.

Zeer laag

  • er is zeer lage zekerheid dat het ware effect van behandeling dichtbij het geschatte effect van behandeling ligt;
  • de literatuurconclusie is zeer onzeker.

 

Bij het beoordelen (graderen) van de kracht van het wetenschappelijk bewijs in richtlijnen volgens de GRADE-methodiek spelen grenzen voor klinische besluitvorming een belangrijke rol (Hultcrantz, 2017). Dit zijn de grenzen die bij overschrijding aanleiding zouden geven tot een aanpassing van de aanbeveling. Om de grenzen voor klinische besluitvorming te bepalen moeten alle relevante uitkomstmaten en overwegingen worden meegewogen. De grenzen voor klinische besluitvorming zijn daarmee niet één op één vergelijkbaar met het minimaal klinisch relevant verschil (Minimal Clinically Important Difference, MCID). Met name in situaties waarin een interventie geen belangrijke nadelen heeft en de kosten relatief laag zijn, kan de grens voor klinische besluitvorming met betrekking tot de effectiviteit van de interventie bij een lagere waarde (dichter bij het nuleffect) liggen dan de MCID (Hultcrantz, 2017).

 

Overwegingen (van bewijs naar aanbeveling)

Om te komen tot een aanbeveling zijn naast (de kwaliteit van) het wetenschappelijke bewijs ook andere aspecten belangrijk en worden meegewogen, zoals aanvullende argumenten uit bijvoorbeeld de biomechanica of fysiologie, waarden en voorkeuren van patiënten, kosten (middelenbeslag), aanvaardbaarheid, haalbaarheid en implementatie. Deze aspecten zijn systematisch vermeld en beoordeeld (gewogen) onder het kopje ‘Overwegingen’ en kunnen (mede) gebaseerd zijn op expert opinion. Hierbij is gebruik gemaakt van een gestructureerd format gebaseerd op het evidence-to-decision framework van de internationale GRADE Working Group (Alonso-Coello, 2016a; Alonso-Coello 2016b). Dit evidence-to-decision framework is een integraal onderdeel van de GRADE methodiek.

 

Formuleren van aanbevelingen

De aanbevelingen geven antwoord op de uitgangsvraag en zijn gebaseerd op het beschikbare wetenschappelijke bewijs en de belangrijkste overwegingen, en een weging van de gunstige en ongunstige effecten van de relevante interventies. De kracht van het wetenschappelijk bewijs en het gewicht dat door de werkgroep wordt toegekend aan de overwegingen, bepalen samen de sterkte van de aanbeveling. Conform de GRADE-methodiek sluit een lage bewijskracht van conclusies in de systematische literatuuranalyse een sterke aanbeveling niet a priori uit, en zijn bij een hoge bewijskracht ook zwakke aanbevelingen mogelijk (Agoritsas, 2017; Neumann, 2016). De sterkte van de aanbeveling wordt altijd bepaald door weging van alle relevante argumenten tezamen. De werkgroep heeft bij elke aanbeveling opgenomen hoe zij tot de richting en sterkte van de aanbeveling zijn gekomen.

In de GRADE-methodiek wordt onderscheid gemaakt tussen sterke en zwakke (of conditionele) aanbevelingen. De sterkte van een aanbeveling verwijst naar de mate van zekerheid dat de voordelen van de interventie opwegen tegen de nadelen (of vice versa), gezien over het hele spectrum van patiënten waarvoor de aanbeveling is bedoeld. De sterkte van een aanbeveling heeft duidelijke implicaties voor patiënten, behandelaars en beleidsmakers (zie onderstaande tabel). Een aanbeveling is geen dictaat, zelfs een sterke aanbeveling gebaseerd op bewijs van hoge kwaliteit (GRADE gradering HOOG) zal niet altijd van toepassing zijn, onder alle mogelijke omstandigheden en voor elke individuele patiënt.

 

Implicaties van sterke en zwakke aanbevelingen voor verschillende richtlijngebruikers

 

Sterke aanbeveling

Zwakke (conditionele) aanbeveling

Voor patiënten

De meeste patiënten zouden de aanbevolen interventie of aanpak kiezen en slechts een klein aantal niet.

Een aanzienlijk deel van de patiënten zouden de aanbevolen interventie of aanpak kiezen, maar veel patiënten ook niet. 

Voor behandelaars

De meeste patiënten zouden de aanbevolen interventie of aanpak moeten ontvangen.

Er zijn meerdere geschikte interventies of aanpakken. De patiënt moet worden ondersteund bij de keuze voor de interventie of aanpak die het beste aansluit bij zijn of haar waarden en voorkeuren.

Voor beleidsmakers

De aanbevolen interventie of aanpak kan worden gezien als standaardbeleid.

Beleidsbepaling vereist uitvoerige discussie met betrokkenheid van veel stakeholders. Er is een grotere kans op lokale beleidsverschillen. 

 

Organisatie van zorg

In de knelpuntenanalyse en bij de ontwikkeling van de richtlijnmodule is expliciet aandacht geweest voor de organisatie van zorg: alle aspecten die randvoorwaardelijk zijn voor het verlenen van zorg (zoals coördinatie, communicatie, (financiële) middelen, mankracht en infrastructuur). Randvoorwaarden die relevant zijn voor het beantwoorden van deze specifieke uitgangsvraag zijn genoemd bij de overwegingen. Meer algemene, overkoepelende, of bijkomende aspecten van de organisatie van zorg worden behandeld in de module Organisatie van zorg.

 

Commentaar- en autorisatiefase

De conceptrichtlijnmodule werd aan de betrokken (wetenschappelijke) verenigingen en (patiënt) organisaties voorgelegd ter commentaar. De commentaren werden verzameld en besproken met de werkgroep. Naar aanleiding van de commentaren werd de conceptrichtlijnmodule aangepast en definitief vastgesteld door de werkgroep. De definitieve richtlijnmodule werd aan de deelnemende (wetenschappelijke) verenigingen en (patiënt) organisaties voorgelegd voor autorisatie en door hen geautoriseerd dan wel geaccordeerd.

 

Adaptatie

Een aantal modules van deze richtlijn betreft een adaptatie van modules van de World Health Organization (WHO)-richtlijn ‘Global guidelines for the prevention of surgical site infection’ (WHO, 2018), te weten:

  • Module Normothermie
  • Module Immunosuppressive middelen
  • Module Glykemische controle
  • Module Antimicrobiële afdichtingsmiddelen
  • Module Wondbeschermers bij laparotomie
  • Module Preoperatief douchen
  • Module Preoperatief verwijderen van haar
  • Module Chirurgische handschoenen: Vervangen en type handschoenen
  • Module Afdekmaterialen en operatiejassen

Methode

  • Uitgangsvragen zijn opgesteld in overeenstemming met de standaardprocedures van het Kennisinstituut van de Federatie Medisch Specialisten.
  • De inleiding van iedere module betreft een korte uiteenzetting van het knelpunt, waarbij eventuele onduidelijkheid en praktijkvariatie voor de Nederlandse setting wordt beschreven.
  • Het literatuuronderzoek is overgenomen uit de WHO-richtlijn. Afhankelijk van de beoordeling van de actualiteit van de richtlijn is een update van het literatuuronderzoek uitgevoerd.
  • De samenvatting van de literatuur is overgenomen van de WHO-richtlijn, waarbij door de werkgroep onderscheid is gemaakt tussen ‘cruciale’ en ‘belangrijke’ uitkomsten. Daarnaast zijn door de werkgroep grenzen voor klinische besluitvorming gedefinieerd in overeenstemming met de standaardprocedures van het Kennisinstituut van de Federatie Medisch Specialisten, en is de interpretatie van de bevindingen primair gebaseerd op klinische relevantie van het gevonden effect, niet op statistische significantie. In de meta-analyses zijn naast odds-ratio’s ook relatief risico’s en risicoverschillen gerapporteerd.
  • De beoordeling van de mate van bewijskracht is overgnomen van de WHO-richtlijn, waarbij de beoordeling is gecontroleerd op consistentie met de standaardprocedures van het Kennisinstituut van de Federatie Medisch Specialisten (GRADE-methode; http://www.gradeworkinggroup.org/). Eventueel door de WHO gerapporteerde bewijskracht voor observationele studies is niet overgenomen indien ook gerandomiseerde gecontroleerde studies beschikbaar waren.
  • De conclusies van de literatuuranalyse zijn geformuleerd in overeenstemming met de standaardprocedures van het Kennisinstituut van de Federatie Medisch Specialisten.
  • In de overwegingen heeft de werkgroep voor iedere aanbeveling het bewijs waarop de aanbeveling is gebaseerd en de aanvaardbaarheid en toepasbaarheid van de aanbeveling voor de Nederlandse klinische praktijk beoordeeld. Op basis van deze beoordeling is door de werkgroep besloten welke aanbevelingen ongewijzigd zijn overgenomen, welke aanbevelingen niet zijn overgenomen, en welke aanbevelingen (mits in overeenstemming met het bewijs) zijn aangepast naar de Nederlandse context. ‘De novo’ aanbevelingen zijn gedaan in situaties waarin de werkgroep van mening was dat een aanbeveling nodig was, maar deze niet als zodanig in de WHO-richtlijn was opgenomen. Voor elke aanbeveling is vermeld hoe deze tot stand is gekomen, te weten: ‘WHO’, ‘aangepast van WHO’ of ‘de novo’.

Voor een verdere toelichting op de procedure van adapteren wordt verwezen naar de Bijlage Adapteren.

 

Literatuur

Agoritsas T, Merglen A, Heen AF, Kristiansen A, Neumann I, Brito JP, Brignardello-Petersen R, Alexander PE, Rind DM, Vandvik PO, Guyatt GH. UpToDate adherence to GRADE criteria for strong recommendations: an analytical survey. BMJ Open. 2017 Nov 16;7(11):e018593. doi: 10.1136/bmjopen-2017-018593. PubMed PMID: 29150475; PubMed Central PMCID: PMC5701989.

 

Alonso-Coello P, Schünemann HJ, Moberg J, Brignardello-Petersen R, Akl EA, Davoli M, Treweek S, Mustafa RA, Rada G, Rosenbaum S, Morelli A, Guyatt GH, Oxman AD; GRADE Working Group. GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 1: Introduction. BMJ. 2016 Jun 28;353:i2016. doi: 10.1136/bmj.i2016. PubMed PMID: 27353417.

 

Alonso-Coello P, Oxman AD, Moberg J, Brignardello-Petersen R, Akl EA, Davoli M, Treweek S, Mustafa RA, Vandvik PO, Meerpohl J, Guyatt GH, Schünemann HJ; GRADE Working Group. GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 2: Clinical practice guidelines. BMJ. 2016 Jun 30;353:i2089. doi: 10.1136/bmj.i2089. PubMed PMID: 27365494.

 

Brouwers MC, Kho ME, Browman GP, Burgers JS, Cluzeau F, Feder G, Fervers B, Graham ID, Grimshaw J, Hanna SE, Littlejohns P, Makarski J, Zitzelsberger L; AGREE Next Steps Consortium. AGREE II: advancing guideline development, reporting and evaluation in health care. CMAJ. 2010 Dec 14;182(18):E839-42. doi: 10.1503/cmaj.090449. Epub 2010 Jul 5. Review. PubMed PMID: 20603348; PubMed Central PMCID: PMC3001530.

 

Hultcrantz M, Rind D, Akl EA, Treweek S, Mustafa RA, Iorio A, Alper BS, Meerpohl JJ, Murad MH, Ansari MT, Katikireddi SV, Östlund P, Tranæus S, Christensen R, Gartlehner G, Brozek J, Izcovich A, Schünemann H, Guyatt G. The GRADE Working Group clarifies the construct of certainty of evidence. J Clin Epidemiol. 2017 Jul;87:4-13. doi: 10.1016/j.jclinepi.2017.05.006. Epub 2017 May 18. PubMed PMID: 28529184; PubMed Central PMCID: PMC6542664.

 

Medisch Specialistische Richtlijnen 2.0 (2012). Adviescommissie Richtlijnen van de Raad Kwalitieit. http://richtlijnendatabase.nl/over_deze_site/over_richtlijnontwikkeling.html

 

Neumann I, Santesso N, Akl EA, Rind DM, Vandvik PO, Alonso-Coello P, Agoritsas T, Mustafa RA, Alexander PE, Schünemann H, Guyatt GH. A guide for health professionals to interpret and use recommendations in guidelines developed with the GRADE approach. J Clin Epidemiol. 2016 Apr;72:45-55. doi: 10.1016/j.jclinepi.2015.11.017. Epub 2016 Jan 6. Review. PubMed PMID: 26772609.

 

Schünemann H, Brożek J, Guyatt G, et al. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. The GRADE Working Group, 2013. Available from http://gdt.guidelinedevelopment.org/central_prod/_design/client/handbook/handbook.html.

 

World Health Organization. Global guidelines for the prevention of surgical site infection,

second edition. Geneva: World Health Organization; 2018. (https://www.who.int/publications/i/item/9789241550475, accessed 12 June 2023).

 

Zoekverantwoording

Zoekacties zijn opvraagbaar. Neem hiervoor contact op met de Richtlijnendatabase.

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Huiddesinfectie